The overall objective of the proposed research is to improve the medical prevention of nephrolithiasis by developing a new clinical assay that can predict the recurrence of kidney stones in patients with this chronic and costly disease. Currently available technology, consisting of routine urine chemistry measurements, is a poor predictor of a patient's risk for developing recurrent stones. Those patients destined to recur would benefit from tests that could identify them in advance so that therapy or prevention could be implemented early. We have found two proteins that are known inhibitors of calcium oxalate crystal growth to be significantly altered in the urine of stone formers. We have developed a western blotting method to measure various forms of these proteins in urine. Preliminary studies have shown that the combination of these protein measurements with standard urine chemistry risk factors vastly improved the discrimination of stone formers from non-stone formers compared to standard urine chemistries alone. Our hypothesis is that alterations in these proteins in the urine of kidney stone patients may serve as a marker of stone disease activity or vulnerability to recurrence. We predict that the protein patterns may change in response to therapies that reduce stone formation. We propose to use our current western blotting method to look for changes in these proteins in the urine of calcium stone formers before and after treatment with two medications commonly used to prevent recurrent nephrolithiasis. We will also develop a quantitative western blotting assay in order to improve the accuracy and stability of our method of analysis. In Phase II we will test whether these measurements can be used to identify kidney stone patients at risk for recurrence by looking for differences in these proteins between patients receiving active drug therapy who have or have not had a relapse of stones.